Immediate Hypersensitivity: Mechanisms, Manifestations, Management Flashcards
What factors contribute to allergic disease?
- genetics
- environment-pollution
- changes in lifestyle: hygiene hypothesis
- occupational exposures
- certain medications
Urban lifestyles are more hygienic and cause a shift from ___ to ___ phenotype.
TH1 –> TH2
What are the 3 types of immediate hypersensitivity reactions?
- Immunologic: IgE-mediated
- Immunologic: Non-IgE-mediated (substance works directly on mast cells)
- Non-immunologic
Describe Immunologic Non-IgE mediated reactions
- substance acts directly on mast cells to cause degranulation
- IgE not required
- no prior exposure necessary (sensitization not necessary)
- ex: drugs: muscle relaxants, antibiotics, RCA (contrast agents), protamine, ASA, NSAIDs
What are examples of non-immunologic reactions?
- compliment mediated: C3a, C5a
- reactions to blood products
- reactions to dialysis membranes
- IgE-mediated:
- Intermediate:
- Non-IgE mediated:
- Oral allergy syndrome, anaphylaxis, urticaria
- eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, atopic dermatitis
- protein-induced, enterocolitis, protein-induced, enteropathy, dermatitis, herpetiforms
What signals from T helper cells (Th) to B cells result in IgE production?
- CD40
- IL-4
Describe IgE-mediated reactions:
- requires prior exposure (initiates IgE isotype switch)
- allergen-specific IgE produced by plasma cells, released to circulation
- binds high affinity receptors on mast cells + basophils
- next exposure to allergen results in mast cell degranulation
Describe IgE:
- binds Fc receptors on basophils and mast cells
- half-life: few days
- protected from proteases by binding to these cells
- sensitization can lasts for months (bound to cells)
- detected by skin prick test or radioallergosorbant test (RAST)
CT Mast Cell vs. Mucosal Mast Cell:
CT Mast cell:
- ubiquitous-long lived >40 days
- 3x10^4 IgE receptors
- high histamine content
- heparin and high levels of tryptase
Mucosal Mast cell: -gut and lung -T cell dependent -short lived <40 days -25x10^5 IgE receptors -lower histamine content chondroitin sulphate -lower tryptase
Describe the order of IgE-dependent release of mediators from mast cells:
Immediate release: histamine, TNF-a, proteases, heparin –> sneezing, nasal congestion, itchy/runny nose, watery eyes, wheezing, bronchoconstriction
Minutes: lipid mediators, prostaglandins, leukotrienes (wheezing, bronchoconstriction)
hours: cytokines produced: IL-4, IL-13–> mucus production, eosinophil recruitment
What are the 3 classes of mediators derived from mast cells?
what various outcomes result from their release?
- preformed, stored in granules (histamine)
- newly formed: leukotrienes, prostaglandins, platelet activating factor
- cytokines produced by activated mast cells/basophils: TNF, IL3, IL4, IL5, IL13, chemokines
outcomes:
-smooth m. contraction, mucus secretion, bronchial spasm, vasodilation, vascular permeability, edema
What does histamine do?
- non-life-threatening aspects of allergic reaction
- inc vascular permeability–> edema
- vasodilation
- constricts bronchial sm. m.
- stimulates secretion from nasal, bronchial, gastric glands
- hives, conjunctivitis, rhinitis
effects of histamine on:
- skin
- eye
- nose
- lung
- skin: wheal, erythema, pruritis
- eye: conjunctivitis, erythema, pruritis
- nose: nasal discharge, sneeze, pruritis
- lung: bronchospasm of sm. m.
What does PAF (platelet activating factor) do?
-life-threatening manifestations of immediate hypersensitivity (lethal)
- hypotension
- increased vasc. permeability
- impaired myocardial contractility
- bronchospasm
- coagulopathy
